The development of the sensory and motor components of the peripheral nervous system (PNS) is tightly regulated by a complex network of signaling molecules. These signaling molecules control cellular processes such as cell migration, proliferation, differentiation, fate specification, axon guidance, and the establishment of specific synapses. In the central nervous system, signal transduction through members of the erbB family, including the epidermal growth factor receptor (EGFR), influences glial and neuronal proliferation, differentiation, fate acquisition, neurite outgrowth and survival. Loss of EGFR results in defective neuronal migration in the CNS as well as abnormal proliferation, differentiation, and maintenance of the cutaneous epithelium. Signal transduction through EGFR family members, all of which are expressed in the PNS, is vital for normal development of both motor and sensory neurons. This proposal is designed to test the hypotheses that EGFR signaling is also required for proper development of the peripheral nervous system and that interactions between neural and target cells regulate PNS development. Specific aim 1. To determine the role of EGFR in the development of the PNS by examining the effects of loss of EGFR on innervation of the skin during development using EGFR homozygous null mice. Specific aim 2. To determine whether developmental regulation of the PNS by EGFR is cell autonomous or regulated by the expression of EGFR in the target tissue. Specific Aim 3. To identify downstream effector genes through which EGFR regulates the development of the PNS.